Basal cell carcinoma (BCC) is the most common malignancy in the United States; however, it has been[unreadable] relatively understudied in epidemiologic research. Temporal trends indicate that BCC incidence is increasing[unreadable] overall, in young adults, and especially in young women. Data from "early onset" cases support the concept[unreadable] that there are at least two different subgroups accounting for BCCs in individuals below the age of 40?a[unreadable] group with single tumors whose incidence is increasing, presumably due to environmental factors, and a[unreadable] group with multiple tumors whose incidence is stable and who probably have hereditary predisposition to[unreadable] BCCs. The purpose of this study is to assess genetic and environmental risk factors for early onset BCCs[unreadable] and explore the interaction between these factors. This study is an outgrowth of our previous work showing[unreadable] that the PTCH gene underlies both hereditary and sporadic BCCs but applies and extends this work at a[unreadable] population level, with careful consideration of environmental contributions to the disease incidence.[unreadable] Five hundred cases with early onset BCC and 500 controls with benign skin conditions will be recruited from[unreadable] the Yale dermatopathology database for interviews and collection of biological samples. Questionnaire data[unreadable] will be used to assess potential environmental factors that might be related to the increased incidence,[unreadable] especially artificial tanning, excessive solar radiation exposure, smoking, and obesity. The interaction[unreadable] between these environmental variables and genetic variants of MC1R, known to relate to skin cancer[unreadable] susceptibility, will be assessed. Tumors from selected subjects in whom BCC risk appears to be related[unreadable] strongly to a particular environmental exposure will undergo sequencing of the PTCH gene to relate the[unreadable] reported exposure to "signature mutations" in DNA. Subjects with large numbers of BCCs or particularly[unreadable] early age of onset of BCCs will have detailed genetic studies to determine if they have a known hereditary[unreadable] disorder, and if not, to identify novel BCC predisposition genes.[unreadable] Risk factor data are needed to serve as a basis to guide preventive interventions. For example, strong[unreadable] evidence that tanning bed use is an important etiologic factor in early onset BCC, with supporting evidence[unreadable] showing mutational spectra consistent with UVB mutations, could form the basis for stronger legislation to[unreadable] prevent tanning bed use by minors. Alternatively, if smoking or other risk factors are more strongly[unreadable] associated, this suggests a different intervention strategy to reduce the disease. Identification of underlying[unreadable] predisposition genes may help target efforts at prevention to particular genetic subgroups. Thus, this[unreadable] etiologic work is highly and immediately translatable into preventive interventions aimed at reducing the[unreadable] incidence of this exceedingly common malignancy.